The relationship between the actions of glutathione (GHS) and Interleukin-2 was examined on murine cytotoxic T-cells. We found that the binding, internalization, and degradation of IL-2 were regulated by the duration of GSH treatment of CTLL-2 and CT-4R cells. Northern blot analysis of mRNA of IL-2RNA of IL-2Rp55 and IL-2Rp70, the two major components of the high affinity IL-2 receptors, showed that both the IL-2Rp55 mRNA and the IL-2Rp70 mRNA increased 6 h after GSH treatment and then declined to control level. After removing surface IL-2 receptors by trypsin treatment, we found that the reappearance of IL-2 receptors was faster and reached a higher level in GSH treated than untreated cells. GSH also shortened the half -life (from 5 h to 3 h) and thus increased the turnover of surface high affinity IL-2 receptors. These results suggest that GSH may regulate the actions of IL-2 by enhancing the synthesis and turnover of IL-2 receptors.